Chlorinated hydrocarbons and perhaps other xenobotic compounds interfere with the biochemical action of selenium, thus potentiating selenium-vitamin E deficiency in circumstances of subadequate intake of these nutrients. The selenium- and vitamin E-deficient chick has been well estabished in this laboratory as a useful animal model in studies of the biochemical modes of action of selenium and vitamin E. We propose to use the chick to determine the biochemical basis for the interaction of polychlorinated biophenyls (PCBs), selenium and vitamin E through investigations on the interrelationships of these nutrients with hepatic microsomal oxidative drug metabolism. Specifically, we propose to (a) determine whether selenium and vitamin E are required for optimal induction of drug metabolism, (b) determine whether induction of microsomal drug-metabolizing enzymes by PCBs modifies the subcellular distribution and/or turnover rate of selenium, (c) determine whether microsomal electron transport reactions increase the intercellular need for selenium and/or vitamin E-dependent factors, and (d) determine whether superoxide dismutase activties are influenced by dietary selenium and/or vitamin E. We will employ established biochemical techniques including determinations of hepatic microsomal mixed-function oxygenases and cytochrome P450, glutathione peroxidase, superoxide dismutase, cell fraction marker enzymes, lipid peroxidation by the thiobarbituric acid and diene conjugation absorbance methods, and measurements of subcellullr localization and turnover of selenium using radioisotopic labeling and electron microprobe analysis. We will also determine whether the phenomenon of potentiation of Se-Vitamin E deficiency by dietary PCBs occurs in the rat, using 10 week growth and erythrocyte glutathione peroxidase as assay techniques. Because all biochemical studies will utilize nutritionally controlled and monitored animals, results obtained will be evaluated relative to the performance of the intact animal.